芹菜素混合胶束的制备及其降血糖研究  

Preparation of apigenin mixed micelles for the treatment of mellitus

作　　者：华丽萍 翟競 HUA Liping;ZHAI Jing(Pharmacy Department,Wujin Hospital of Traditional Chinese Medicine,Changzhou,Jiangsu 213161,China;Department of Gastrointestinal Oncology,Jiangsu Provincial Hospital of Traditional Chinese Medicine,Nanjing,Jiangsu 210004,China)

机构地区：[1]常州市武进中医医院药剂科,江苏常州213161 [2]江苏省中医院消化系肿瘤外科,江苏南京210004

出　　处：《安徽医药》2025年第5期908-913,I0001,I0002,共8页Anhui Medical and Pharmaceutical Journal

基　　金：国家自然科学基金项目(82003180)。

摘　　要：目的制备包封芹菜素(API)的普朗尼克105(P105)和聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物的混合胶束(API-MPMs),对其主要性质进行表征,并进行药效学和药动学评价。方法2023年4―12月,以胶束粒径、载药量和包封率为评价指标,优选最佳载体比例,并用透射电镜观察优选处方的胶束结构,透析袋法考察胶束的体外释放;通过大鼠灌胃给药后,对芹菜素原料药和API-MPMs的口服生物利用度进行考察,随后考察芹菜素原料药和API-MPMs对糖尿病小鼠的降糖和肝脏保护作用,并监测相关糖脂代谢指标,最后考察胶束的稳定性。结果当Soluplus和P105比例为3∶1时,制备得到的胶束载药量和包封率最高,分别为(7.8±0.11)%和(71.3±0.08)%;透射电镜显示所制备的胶束呈圆球形且粒径均一;药动学实验结果表明API-MPMs可以显著提高药物的生物利用度,血药达峰浓度(C_(max))为(211.38±34.32)mg/L,血药浓度-时间曲线下面积(AUC_(0-t))为(2477.17±208.15)h·mg^(-1)·L^(-1);药效学实验表明API-MPMs可以显著降低糖尿病小鼠的血糖,血糖由(9.34±1.44)mmol/L降低至(7.27±1.89)mmol/L,并可以改善其肝脏受损情况和糖脂代谢情况,其中三酰甘油(TG)、总胆固醇(TC)降低,胰岛素(INS)值显著升高,超氧化物歧化酶(SOD)和血红素氧合酶1(HO-1)呈现一定的上升,丙二醛(MDA)呈现一定的下降;稳定性实验表明此胶束在水中、模拟胃肠道环境及模拟生理环境下稳定性良好。结论制备P105和Soluplus为混合载体的芹菜素胶束,可以提高芹菜素的溶解度和生物利用度,并显著改善了芹菜素的治疗效果。Objective To prepare Apigenin(API)P105/Soluplus mixed micelles,characterize main properties and evaluate pharmacodynamics and pharmacokinetics of mixed micelles.Methods From April to December 2023,particle size,drug loading and encapsulation efficiency were used as evaluation indicators to optimize the carrier ratio of the formulation.The structure of optimized mixed micelles was observed by using transmission electron microscopy,and the in vitro release of mixed micelles was investigated by using dialysis bag method.The bioavailability of API and API-MPMs were compared by oral administration in rats.Subsequently,the effects of API and API-MPMs on diabetic mice were analyzed and glucolipid metabolism related indicators were determined at the same time.Finally,the stability of API-MNMs was conducted by detecting particle size.Results The optimized ratio of Soluplus/P105 was 3∶1,and the obtained micelles exhibited the highest drug loading and encapsulation efficiency,which reached to(7.8±0.11)%and(71.3±0.08)%,respectively.Transmission electron microscopy showed that the micelles were spherical and possessed the uniform particle size.Pharmacokinetics results in rats showed that the micelles could significantly increase the bioavailability of the drug.C_(max) was(211.38±34.32)mg/L and AUC_(0-t) was(2477.17±208.15)h·mg^(-1)·L^(-1).Pharmacodynamics experiments showed that the API-MPMs could significantly reduce the blood sugar in diabetes mice,lowering the blood sugar from(9.34±1.44)mmol/L to(7.27±1.89)mmol/L and repair the damaged liver and regulate the glycolipid metabolism,in which TC and TG values decreased,INS values increased significantly,SOD and HO-1 values increased to a certain extent.The stability experiment showed that the mixed micelles were relatively stable in water,simulated physiological conditions and serum.Conclusion API-P105/Soluplus mixed micelles can increase the solubility and bioavailability of API,and significantly improve the therapeutic efficacy of API.

关 键 词：芹菜素 混合胶束 生物利用度 糖尿病 

分 类 号：R283.6[医药卫生—中药学]